NK Cells Infusions With Irinotecan, Temozolomide, and Dinutuximab

NCT04211675 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00000476
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1 study with Phase 2 expansion cohort. Phase 1 will assess the safety and tolerability of universal donor TGFβi NK Cell in combination with irinotecan, temozolomide, and dinituximab. The phase 2 of the study will estimate the response to treatment.

Conditions

Relapsed Neuroblastoma; Refractory Neuroblastoma

Outcome Measures

Primary Outcomes (4)

• NK cells safety and tolerability: Number of participants with treatment-related adverse events and toxicities

  Number of participants with treatment-related adverse events and toxicities as assessed by CTCAE v4.0

  12 months

• Response to NK Cell treatment as determine by CT/MRI imaging

  To estimate the response to treatment, as determined by disease status evaluated using CT/MRI scans through the measuring tool RECIST.

  24 months

• Response to NK Cell treatment as determine by MIBG scans imaging

  To estimate the response to treatment, as determined by disease status evaluated using MIBG scans through the Curie score system.

  24 months

• Response to NK Cell treatment as determine by bone marrow aspiration

  To estimate the response to treatment, as determined by disease status evaluated using bone marrow aspiration and biopsy through H\&E stain. RECIST.

  24 months

Secondary Outcomes (1)

• Toxicity Definition of NK cells

  36 months

Other Outcomes (4)

• Assessment of the phenotype of expanded NK cells for neuroblastoma patients

  36 months

• Assessment of function of expanded NK cells for neuroblastoma patients

  36 months

• In vivo persistence of NK cells after adoptive transfer.

  36 months

Study Arms (1)

Treatment

OTHER

The planned therapy will involve 6 cycles of 21 days each consisting of irinotecan, temozolomide, dinutuximab, sargramostim, and natural killer (NK) cells. Treatment cycles will be repeated every 21 days based upon disease response and toxicity criteria. Tumor response will be assessed after Cycles 2, 4 and 6. Patients who do not experience dose-limiting toxicities and achieve complete response, partial response or stable disease may continue to receive the assigned therapy.

Biological: Natural Killer Cells; Drug: Temozolomide; Drug: Irinotecan; Drug: Dinutuximab; Drug: Sargramostim

Interventions

Natural Killer Cells BIOLOGICAL

NK cells dose 1x 108 cells/ kg on day 8 of each cycle

Treatment

Temozolomide DRUG

Temozolomide 100mg/m2/dose PO or IV daily on Days 1-5; if given orally, must be at least one hour prior to Irinotecan. For patients whose body surface area is \<0.5m2, temozolomide dosing is based on body weight in (kg), at a dose of 3.3 mg/kg/dose.

Also known as: Temodar

Treatment

Irinotecan DRUG

Irinotecan 50mg/m2/dose IV daily on Days 1-5

Also known as: Camptosar

Treatment

Dinutuximab DRUG

Dinutuximab 17.5mg/m2/dose IV daily on Days 2-5

Treatment

Sargramostim DRUG

Sargramostim 250mcg/m2/dose subcutaneous daily on Days 6-12

Also known as: Leukine

Treatment

Eligibility Criteria

• Age: Up to 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Less than 30 years of age when registered on the study.
• Patients must have a histologic verification of neuroblastoma (NBL) or ganglioneuroblastoma or NBL cells in bone marrow with or without elevated urine catecholamines.
• Life expectancy \>2 months, AND one of the following:
• Recurrent disease; or
• First episode of progressive disease (new lesion, increase in size, previous negative bone marrow) during initial multi-drug, induction myelosuppressive therapy; or
• Primary resistant/refractory disease (partial, mixed, stable response criteria met) after completing at least 4 cycles of induction multi-drug induction chemotherapy
• One of the following:
• Patients must have measurable or evaluable tumor defined as: a) Measurable tumor on MRI or CT obtained within 4 weeks prior to study entry; Measurable is defined as ≥ 10mm in at least one dimension AND that has positive uptake on I-123 MIBG scan ("MIBG avid") or demonstrates increased FDG uptake on 18F-FDG PET-CT or PET-MRI ("PET-avid"); OR b) Evaluable tumor by I-123 MIBG scan within 4 weeks prior to study entry, defined as positive uptake at a minimum of one site;
• Measurable or evaluable disease must represent recurrent disease after therapy completion or progressive disease on therapy or refractory disease during induction;
• Patients with refractory disease that are not avid on MIBG scan and do not have increased FDG uptake on PET must have biopsy proven viable NBL;
• New soft tissue sites that are MIBG avid or PET avid do not require biopsy as long as initial histologically-confirmed NBL diagnosis prior to current therapy
• Patients must have progressed during or following completion of frontline therapy. Agents considered to be a part of frontline therapy would include chemotherapy, radiation therapy, autologous stem cell transplantation, retinoids, immunotherapy with anti GD2 agents, cellular therapies, or I-131 MIBG, and frontline therapy is defined as any combination of these agents defined in published regimens or current cooperative group clinical trials for the successful treatment of that cancer. Therapy may not have been received more recently than the timeframes defined below:
• Myelosuppressive chemotherapy: At least 14 days since completion of myelosuppressive therapy
• Biologic: At least 7 days since completion of therapy with non-myelosuppressive biologic or retinoid
• Radiation: At least 4 weeks since completion of radiation to any site identified as a target lesion. Palliative radiation is allowed to sites not used to measure response

You may not qualify if:

• Patients who are pregnant or breastfeeding
• Patients with elevated catecholamines (\>2x ULN) only.
• Patients must not have received 0.5 mg/ kg/ day (prednisone equivalent) doses of systemic steroids for at least 7 days prior to enrollment.
• Patients must not have received CYP3A4 inducer or inhibitor for at least 7 days prior to study enrollment.
• Patients must not have been diagnosed with any other malignancy.
• Patients must not have \> Grade 2 diarrhea.
• Patients must not have uncontrolled infection.
• Patients with history of Grade 4 allergic reactions to anti-GD2 antibodies or reactions that required discontinuation of anti-GD2 therapy.

Sponsors & Collaborators

• Nationwide Children's Hospital: lead

Study Sites (1)

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

MeSH Terms

Conditions

Neuroblastoma

Interventions

IL32 protein, human; Temozolomide; Irinotecan; dinutuximab; sargramostim

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids

Study Officials

• Mark Ranalli, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melinda Triplet, RN

CONTACT

614-722-6039; Melinda.Triplet@nationwidechildrens.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2019
• First Posted: December 26, 2019
• Study Start: September 1, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: May 13, 2025

Record last verified: 2025-05

Locations

US (1)